Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, East Geelong, VIC 3220, Australia.
Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou 325060, China.
Int J Mol Sci. 2024 Sep 2;25(17):9535. doi: 10.3390/ijms25179535.
Increasing numbers of reports have revealed novel catalytically active cryptic guanylate cyclases (GCs) and adenylate cyclases (ACs) operating within complex proteins in prokaryotes and eukaryotes. Here we review the structural and functional aspects of some of these cyclases and provide examples that illustrate their roles in the regulation of the intramolecular functions of complex proteins, such as the phytosulfokine receptor (PSKR), and reassess their contribution to signal generation and tuning. Another multidomain protein, K uptake permease (AtKUP5), also harbors multiple catalytically active sites including an N-terminal AC and C-terminal phosphodiesterase (PDE) with an abscisic acid-binding site. We argue that this architecture may enable the fine-tuning and/or sensing of K flux and integrate hormone responses to cAMP homeostasis. We also discuss how searches with motifs based on conserved amino acids in catalytic centers led to the discovery of GCs and ACs and propose how this approach can be applied to discover hitherto masked active sites in bacterial, fungal, and animal proteomes. Finally, we show that motif searches are a promising approach to discover ancient biological functions such as hormone or gas binding.
越来越多的报道揭示了新型催化活性的隐秘鸟苷酸环化酶（GCs）和腺苷酸环化酶（ACs），它们在原核生物和真核生物的复杂蛋白质中发挥作用。在这里，我们回顾了其中一些环化酶的结构和功能方面，并提供了一些例子来说明它们在调节复杂蛋白质的分子内功能（如植物磺肽受体（PSKR））中的作用，并重新评估它们在信号产生和调节中的贡献。另一种多结构域蛋白 K 摄取渗透酶（AtKUP5）也包含多个催化活性位点，包括 N 端 AC 和 C 端磷酸二酯酶（PDE），具有脱落酸结合位点。我们认为这种结构可能使 K 通量的微调/感应成为可能，并整合激素对 cAMP 动态平衡的反应。我们还讨论了如何使用基于催化中心保守氨基酸的基序进行搜索，从而发现 GCs 和 ACs，并提出如何将这种方法应用于发现细菌、真菌和动物蛋白质组中迄今被掩盖的活性位点。最后，我们表明，基序搜索是发现激素或气体结合等古老生物功能的一种很有前途的方法。
